ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.4028_4038dup (p.Ala1347delinsGlnLeuTer)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
All of Us Research Program, National Institutes of Health RCV004015147 SCV004832261 uncertain significance Lynch syndrome 2023-08-23 criteria provided, single submitter clinical testing This variant inserts 11 nucleotides in exon 10 of the MSH6 gene, creating a frameshift and premature translation stop signal. This mutant transcript is predicted to escape nonsense-mediated decay and be expressed as a truncated protein lacking 12 residues of the C-terminal region, which contains part of the ATPase and MSH2 binding domains (PMID: 12019211). However, the clinical relevance of the loss of this C-terminal region is not known. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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